Prostate cancer is a major health problem in the United States. There is an urgent need to develop additional, new strategies to prevent the development of this malignancy. The use of food products for cancer prevention is appealing because they are readily available and exhibit little to no toxicity. In particular lyophilized berry preparations can prevent carcinogenesis in animal models, ellagic acid and anthocyanins occurring in berries may be responsible of for this chemopreventive activity, and multiple mechanisms of this effect have been identified. Oral administration of lyophilized berries reduced mammary carcinogenesis in a rat model, indicating that bioactive protective constituents of berries are bioavailable and reach cancer sites via the blood stream. In humans consuming lyophilized black raspberries, ellagic acid and anthocyanins are detectable in urine and blood indicating bioavailability in humans as well. Because these compounds have anti-oxidant and/or anti-inflammatory activity and inflammatory processes and oxidative stress are involved in the etiology of human prostate cancer, lyophilized black raspberries may protect against this malignancy. However, there have been no studies testing the ability of lyophilized berries to inhibit prostate carcinogenesis. This project will test the hypothesis that dietary supplementation with lyophilized black raspberries inhibits the development of prostate cancer in relevant rat models, possibly through a mixture of anti-oxidant and/or anti- inflammatory activity and other anti-cancer mechanisms activity of bioactive berry constituents. Virtually all preclinical data on anticancer effects of black raspberries in other animal models have been developed in rats. Therefore, we will test this hypothesis in proof-of-principle experiments using two well-established and well- characterized rat models of prostate carcinogenesis, one that has been validated for chemoprevention studies and one that uniquely involves an inflammatory component. This dual model approach should importantly allow capturing multiple anticancer mechanisms of black raspberries. The Specific Aims are: (1) Determine whether feeding lyophilized black raspberries reduces prostate cancer incidence or multiplicity and/or reduces tumor growth in the MNU plus testosterone model in Wistar WU rats, a model that does not involve inflammation and is unlikely to involve oxidative stress, but readily progresses to metastatic cancer;and (2) determine whether feeding lyophilized black raspberries reduces prostate cancer incidence or multiplicity, and/or reduces the extent of inflammation and dysplastic lesions in the estradiol plus testosterone model in Noble (NBL) rats, a model that uniquely involves oxidative stress and inflammation, but does not readily progresses to metastatic cancer. We will also save tissues from the studies of Aims 1 and 2 for exploration of effects of feeding black raspberries on markers of oxidative stress, cell proliferation, and apoptosis, as well as measurement of ellagic acid and anthocyanins in prostate tissue. Positive results from the proposed specific aims would provide rationale for further mechanistic studies and clinical trials with prostate cancer patients. PUBLIC HEALTH RELEVANCE: Prostate cancer is a major health problem in the United States. There is an urgent need to develop additional, new strategies to prevent the development of this malignancy. The use of food products for cancer prevention is appealing because they are readily available and exhibit little to no toxicity. Freeze- dried berry preparations can prevent carcinogenesis in animal models and multiple mechanisms of this effect have been identified. Bioactive protective components of berries are taken up in the gut and can reach cancer sites via the blood stream and in humans consuming lyophilized black raspberries, berry-specific compounds are detectable in urine and blood indicating that they are taken up in the gut. However, there have been no studies testing the ability of lyophilized berries to inhibit prostate cancer development. This project will test the hypothesis that dietary supplementation with lyophilized black raspberries inhibit the development of prostate cancer in relevant rat models. We propose to test this hypothesis in experiments with two well-established and well-characterized animal models of prostate carcinogenesis, one that develop progressively malignant cancer and that has been used for chemoprevention studies, and one that uniquely involves inflammation. The specific aims of the project are: (1) Determine whether feeding lyophilized black raspberries reduces prostate cancer in a model in rats that does not involve inflammation, but readily progresses to metastatic cancer. (2) Determine whether feeding lyophilized black raspberries reduces prostate cancer in a rat model that involves inflammation, but does not readily progresses to metastatic cancer. Positive results from the proposed specific aims would provide rationale for further mechanistic and clinical trials with prostate cancer patients.